Hyperoxaluria, including primary and secondary hyperoxaluria, is a disorder characterized by increased urinary oxalate excretion and could lead to recurrent calcium oxalate kidney stones, nephrocalcinosis and eventually end stage renal disease. For secondary hyperoxaluria, high dietary oxalate (HDOx) or its precursors intake is a key reason. Recently, accumulated studies highlight the important role of gut microbiota in the regulation of oxalate homeostasis. However, the underlying mechanisms involving gut microbiota and metabolite disruptions in secondary hyperoxaluria remain poorly understood. Here, we investigated the therapeutic efficacy of fecal microbiota transplantation (FMT) sourced from healthy rats fed with standard pellet diet against urinary oxalate excretion, renal damage and calcium oxalate (CaOx) crystal depositions via using hyperoxaluria rat models. We observed dose-dependent increases in urinary oxalate excretion and CaOx crystal depositions due to hyperoxaluria, accompanied by significant reductions in gut microbiota diversity characterized by shifts in Ruminococcaceae_UCG-014 and Parasutterella composition. Metabolomic analysis validated these findings, revealing substantial decreases in key metabolites associated with these microbial groups. Transplanting microbes from healthy rats effectively reduced HDOx-induced urinary oxalate excretion and CaOx crystal depositions meanwhile restoring Ruminococcaceae_UCG-014 and Parasutterella populations and their associated metabolites. Furthermore, FMT treatment could significantly decrease the urinary oxalate excretion and CaOx crystal depositions in rat kidneys via, at least in part, upregulating the expressions of intestinal barrier proteins and oxalate transporters in the intestine. In conclusion, our study emphasizes the effectiveness of FMT in countering HDOx-induced hyperoxaluria by restoring gut microbiota and related metabolites. These findings provide insights on the complex connection between secondary hyperoxaluria caused by high dietary oxalate and disruptions in gut microbiota, offering promising avenues for targeted therapeutic strategies.

Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the gastrointestinal tract influenced by genetic, environmental, immune, and microbial factors. Reduced gut microbial diversity and elevated proinflammatory bacteria levels in IBD disrupt mucosal immunity, barrier function, and inflammatory pathways. Fecal microbiota transplantation (FMT) is a potential therapy to restore microbial balance. Studies suggest that FMT may induce remission in mild-to-moderate ulcerative colitis but show limited efficacy in Crohn's disease and pouchitis. Donor microbiota colonization correlates with remission, but varied study designs challenge findings. Further research is required to standardize FMT protocols, optimize donor selection, and ensure long-term safety.

Observational studies suggest that gut microbiome (GM) may contribute to acute anterior uveitis (AAU) development, but causality remains unclear. This study was conducted to test whether specific GM taxa were causally associated with AAU.

The GM data were obtained from the DMP, which included 7738 individuals' faecal samples and an analysis of host genotype-taxa abundance associations. The AAU data were derived from the FinnGen Consortium (8624 cases and 473,095 controls). We primarily employed the inverse-variance weighted method, complemented by supplementary sensitivity analyses.

Higher abundance of Lachnospiraceae noname (OR = 0.86, 95% CI 0.81-0.91, P = 5.7 × 10-8), Alistipes finegoldii (OR = 0.87, 95% CI 0.78-0.96, P = 0.008), Erysipelotrichaceae (OR = 0.90, 95% CI 0.81-0.99, P = 0.037), Erysipelotrichia (OR = 0.90, 95% CI 0.81-0.99, P = 0.037), Erysipelotrichales (OR = 0.90, 95% CI 0.81-0.99, P = 0.037), and Bacteroides ovatus (OR = 0.93, 95% CI 0.87-1.00, P = 0.039) predicted a lower AAU risk. Conversely, higher abundance of Bifidobacterium catenulatum (OR = 1.06, 95% CI: 1.02-1.10, P = 0.005), Bacteroides coprocola (OR = 1.11, 95% CI: 1.02-1.21, P = 0.014), Parabacteroides unclassified (OR = 1.12, 95% CI 1.03-1.22, P = 0.010), and Prevotella (OR = 1.15, 95% CI: 1.01-1.29, P = 0.029) predicted a higher AAU risk. The results also showed a reverse causation from AAU to Bifidobacterium catenulatum (OR = 1.39, 95% CI: 1.03-1.86, P = 0.005).

This study suggests that specific GM is causally associated with AAU risk, warranting more mechanistic validation and clinical trials.

The disturbance of gut microbiota and its metabolites are considered to be the causes of ulcerative colitis (UC), which leads to immune abnormalities. Diet is the most important regulator of gut microbiota; therefore, it has a beneficial impact on UC. A novel food ingredient, l-theanine, alters the gut microbiota, thereby regulating gut immunity. However, whether l-theanine prevents UC by altering the gut microbiota, as well as the underlying mechanisms, remains unknown. Here, l-theanine was used to optimize the gut microbiota and its metabolites. Furthermore, to explore the mechanism by which l-theanine prevents UC, an l-theanine fecal microbiota solution was used to prevent dextran sulfate sodium-induced UC via fecal microbiota transplantation. Improvements in the colonic structure, colon histology scores, immune factors (IL-10), and inflammatory factors (IL-1β) demonstrated the preventive effect of l-theanine on UC. The 16S rDNA and metabolomic results showed that tryptophan-, short chain fatty acid-, and bile acid-related microbiota, such as Muribaculaceae, Lachnospiraceae, Alloprevotella, and Prevotellaceae were the dominant. Flow cytometry results showed that l-theanine decreased helper T (Th)1 and Th17 immune responses, and increased Th2 and T-regulatory immune responses via regulation of antigen-presenting cell responses, such as dendritic cells and macrophages. Therefore, l-theanine regulated the immune response of colon CD4 + T cells to dendritic cell and macrophage antigen presentation via tryptophan-, short chain fatty acid-, and bile acid-related microbiota, thereby preventing dextran sulfate sodium-induced UC.

Chemotherapy-induced nausea and vomiting (CINV) significantly impact cancer patients' quality of life. Traditional pharmacological treatments often have limited effectiveness and can cause adverse effects. Acupuncture, a key practice in traditional Chinese medicine (TCM), shows promise as a complementary therapy for CINV. The purpose of this study was to explore the effects and underlying mechanisms of acupuncture in treating CINV.

We employed a multi-faceted approach to comprehensively explore the abnormal performances of CINV model and to elucidate the regulatory effects of acupuncture in treating CINV through the integration of 16S rRNA analysis, serum metabolomics, and network pharmacology.

Acupuncture significantly reduced kaolin consumption, mitigated anorexia, and attenuated body weight loss compared to the model group. Acupuncture was found to modulate the gut microbiota composition, enhancing beneficial taxa and reducing harmful ones. Serum metabolomic analysis revealed significant alterations in metabolic profiles, with acupuncture impacting various metabolites involved in pathways related to fatty acid biosynthesis, urea cycle, and amino acid metabolism. Spearman correlation analysis indicated a significant association between gut microbial taxa and serum metabolites. Furthermore, network pharmacology analysis identified key genes (MAPK1, STAT3, EGFR, AKT1, SRC) and pathways (PI3K/Akt, neuroactive ligand-receptor interaction) associated with the anti-CINV effects of acupuncture. In conclusion, acupuncture holds promise in ameliorating CINV through its multifaceted impact on gut microbiota, serum metabolome, and molecular pathways.

Acupuncture was an adjunctive and important non-drug treatment for CINV, with the protective effects linked to the improvement of gut microbiota disruption and metabolic abnormalities.

Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, is a chronic condition characterized by abnormal immune responses and intestinal inflammation. Emerging evidence highlights the vital role of gut microbiota in IBD's onset and progression. Recent advances have shaped diagnostic and therapeutic strategies, increasingly focusing on microbiome-based personalized care. Methodology: this review covers studies from 2004 to 2024, reflecting the surge in research on luminal microbial ecology in IBD. Human studies were prioritized, with select animal studies included for mechanistic insights. Only English-language, peer-reviewed articles - clinical trials, systematic reviews, and meta-analyses - were considered. Studies without clinical validation were excluded unless offering essential insights. Searches were conducted using PubMed, Scopus, and Web of Science.

we explore mechanisms for managing IBD-related microbiota, including microbial markers for diagnosis and novel therapies such as fecal microbiota transplantation, metabolite-based treatments, and precision microbiome modulation. Additionally, we review technologies and diagnostic tools used to analyze gut microbiota composition and function in clinical settings. Emerging data supporting personalized therapeutic strategies based on individual microbial profiles are discussed.

Standardized microbiome research integration into clinical practice will enhance precision in IBD care, signaling a shift toward microbiota-based personalized medicine.

This article provides an overview of the advancements in the application of fecal microbiota transplantation (FMT) in treating diseases related to intestinal dysbiosis. FMT involves the transfer of healthy donor fecal microbiota into the patient's body, aiming to restore the balance of intestinal microbiota and thereby treat a variety of intestinal diseases such as recurrent Clostridioides difficile infection (rCDI), inflammatory bowel disease (IBD), constipation, short bowel syndrome (SBS), and irritable bowel syndrome (IBS). While FMT has shown high efficacy in the treatment of rCDI, further research is needed for its application in other chronic conditions. This article elaborates on the application of FMT in intestinal diseases and the mechanisms of intestinal dysbiosis, as well as discusses key factors influencing the effectiveness of FMT, including donor selection, recipient characteristics, treatment protocols, and methods for assessing microbiota. Additionally, it emphasizes the key to successful FMT. Future research should focus on optimizing the FMT process to ensure long-term safety and explore the potential application of FMT in a broader range of medical conditions.

Inflammatory bowel disease (IBD) is a chronic recurrent gastrointestinal disease that seriously affects the quality of life of patients around the world. It is characterized by recurrent abdominal pain, diarrhea, and mucous bloody stools. There is an urgent need for more accurate diagnosis and effective treatment of IBD. Accumulated evidence suggests that gut microbiota plays an important role in the occurrence and development of gut inflammation. However, most studies on the role of gut microbiota in IBD have focused on bacteria, while fungal microorganisms have been neglected. Fungal dysbiosis can activate the host protective immune pathway related to the integrity of the epithelial barrier and release a variety of pro-inflammatory cytokines to trigger the inflammatory response. Dectin-1, CARD9, and IL-17 signaling pathways may be immune drivers of fungal dysbacteriosis in the development of IBD. In addition, fungal-bacterial interactions and fungal-derived metabolites also play an important role. Based on this information, we explored new strategies for IBD treatment targeting the intestinal fungal group and its metabolites, such as fungal probiotics, antifungal drugs, diet therapy, and fecal microbiota transplantation (FMT). This review aims to summarize the fungal dysbiosis and pathogenesis of IBD, and provide new insights and directions for further research in this emerging field.

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder with significant extraintestinal manifestations, including cardiovascular derangements. However, the molecular mechanisms underlying the cardiac remodeling and dysfunction remain unclear.

We investigated the effects of chronic colitis on the heart using two mouse models: DSS-induced colitis and Il10 -/- spontaneous colitis. Echocardiography was employed to assess heart function and molecular characterization was performed using bulk RNA-sequencing, RT-qPCR, and western blot.

Both models exhibited significant cardiac impairment, including reduced ejection fraction and fractional shortening as well as increased collagen deposition, inflammation, and myofibril reorganization. Molecular analyses revealed upregulation of fibrosis markers (i.e. COL1A1, COL3A1, Fibronectin) and β-catenin reactivation, indicating a pro-fibrotic cardiac environment. Each model yielded common upregulation of eicosanoid-associated and inflammatory genes ( Cyp2e1 , Map3k6 , Pck1 , Cfd ), and model-specific alterations in pathways regulating cAMP- and cGMP-signaling, arachidonic and linoleic acid metabolism, Cushing syndrome-related genes, and immune cell responses. DSS colitis caused differential regulation of 232 cardiac genes, while Il10 -/- colitis yielded 105 dysregulated genes, revealing distinct molecular pathways driving cardiac dysfunction. Importantly, therapeutic fecal microbiota transplantation (FMT) restored heart function in both models, characterized by reduced fibrosis markers and downregulated pro-inflammatory genes ( Lbp and Cdkn1a in Il10 -/- mice and Fos in DSS mice), while also mitigating intestinal inflammation. Post-FMT cardiac RNA-sequencing revealed significant gene expression changes, with three altered genes in DSS mice and 67 genes in Il10 -/- mice. Notably, Il10 -/- mice showed relatively less cardiac recovery following FMT, highlighting IL-10's cardioprotective and anti-inflammatory contribution.

Our findings elucidate novel insights into colitis-induced cardiac remodeling and dysfunction and suggest that FMT mitigates cardiac dysfunction by attenuating systemic inflammation and correcting gut dysbiosis. This study underscores the need for further evaluation of gut-heart interactions and microbiome-based therapies to improve cardiovascular health in IBD patients.

Clinical data on oral fecal microbiota transplantation (FMT), a promising therapy for Crohn's disease (CD), are limited. Herein, we determined the short-term safety and feasibility of FMT for pediatric patients with active CD.

In this open-label, parallel-group, single-center prospective trial, patients with active CD were treated with oral FMT capsules combined with partial enteral nutrition (PEN) (80%). The control group comprised pediatric patients with active CD treated with PEN (80%) and immunosuppressants. Thirty-three patients (11.6 ± 1.82 years)-17 in the capsule and 16 in the control groups-were analyzed. Data regarding the adverse events, clinical reactions, intestinal microbiome composition, and biomarker parameters were collected and compared post-treatment.

At week 10, the clinical and endoscopic remission rates did not differ between the two groups. By week 10, the mean fecal calprotectin level, C-reactive protein level, erythrocyte sedimentation rate, simple endoscopic score for CD, and pediatric CD activity index decreased significantly in the capsule group (all P < 0.05). The main adverse event was mild-to-moderate constipation. Core functional genera, Agathobacter, Akkermansia, Roseburia, Blautia, Subdoligranulum, and Faecalibacterium, were lacking pre-treatment. Post-treatment, the implantation rates of these core functional genera increased significantly, which positively correlated with the anti-inflammatory factor, interleukin (IL)-10, and negatively correlated with the pro-inflammatory factor, IL-6. The combination of these six functional genera distinguished healthy children from those with CD (area under the curve = 0.96).

Oral FMT capsules combined with PEN (80%) could be an effective therapy for children with active CD. The six core functional genera identified here may be candidate biomarkers for identifying children with CD.

ClinicalTrials.gov, retrospectively registered, ID# NCT05321758, NCT05321745, date of registration: 2022-04-04.

Inflammatory bowel disease (IBD) represents a group of chronic inflammatory disorders of the gastrointestinal tract. Despite substantial advances in our understanding of IBD pathogenesis, the currently available therapeutic options remain limited in their efficacy and often come with significant side effects. Therefore, there is an urgent need to explore novel approaches for the management of IBD. One promising avenue of investigation revolves around the use of histone deacetylase (HDAC) inhibitors, which have garnered considerable attention for their potential in modulating gene expression and curbing inflammatory responses. This review emphasizes the pressing need for innovative drugs in the treatment of IBD, and drawing from a wealth of preclinical studies and clinical trials, we underscore the multifaceted roles and the therapeutic effects of HDAC inhibitors in IBD models and patients. This review aims to contribute significantly to the understanding of HDAC inhibitors' importance and prospects in the management of IBD, ultimately paving the way for improved therapeutic strategies in this challenging clinical landscape.

Aging is associated with intestinal dysbiosis, a condition characterized by diminished microbial biodiversity and inflammation. This leads to increased vulnerability to extraintestinal manifestations such as autoimmune, metabolic, and neurodegenerative conditions thereby accelerating mortality. As such, modulation of the gut microbiome is a promising way to extend healthspan. In this study, we explore the effects of fecal microbiota transplant (FMT) from long-living Ames dwarf donors to their normal littermates, and vice versa, on the recipient gut microbiota and liver transcriptome. Importantly, our previous studies highlight differences between the microbiome of Ames dwarf mice relative to their normal siblings, potentially contributing to their extended lifespan and remarkable healthspan. Our findings demonstrate that FMT from Ames dwarf mice to normal mice significantly alters the recipient's gut microbiota, potentially reprogramming bacterial functions related to healthy aging, and changes the liver transcriptome, indicating improved metabolic health. Particularly, the microbiome of Ames dwarf mice, characterized by a higher abundance of beneficial bacterial families such as Peptococcaceae, Oscillospiraceae, and Lachnospiraceae, appears to play a crucial role in modulating these effects. Alongside, our mRNA sequencing and RT-PCR validation reveals that FMT may contribute to the significant downregulation of p21, Elovl3, and Insig2, genes involved with cellular senescence and liver metabolic pathways. Our data suggest a regulatory axis exists between the gut and liver, highlighting the potential of microbiome-targeted therapies in promoting healthy aging. Future research should focus on functional validation of altered microbial communities and explore the underlying biomolecular pathways that confer geroprotection.

Alteration of the gut microbiota and its metabolites plays a key role in the development of inflammatory bowel disease (IBD). Here, we investigated the mechanism of saponins, a byproduct from quinoa (SQ) processing, in regulating IBD. SQ ameliorated gut microbiota dysbiosis revealed by 16S rRNA sequencing and improved colonic antioxidant activities and barrier integrity in dextran sulfate sodium (DSS)-treated mice. Broad-spectrum antibiotics further proved that the gut-protective effects of SQ were mediated by gut microbiota. Next, fecal microbiota transplantation (FMT) of SQ-induced gut microbiota/metabolites to inoculate DSS-treated mice alleviated colitis significantly. Untargeted metabolomics and lipidomics revealed that ursodeoxycholic acid (UDCA) was enriched as a microbial metabolite after SQ supplementation. UDCA was then found to attenuate DSS-induced colitis in vivo by targeting the TLR4/NF-κB pathway, which was also verified in a Caco-2 cell model treated with a TLR4 agonist/antagonist. Overall, our findings established that gut microbiota-UDCA-TLR4/NF-κB signaling plays a key role in mediating the protective effects of SQ.

The intestinal area is composed of diverse cell types that harmonize gut homeostasis, which is influenced by both endogenous and exogenous factors. Notably, the environment of the intestine is exposed to several types of mechanical forces, including shear stress generated by fluid flow, compression and stretch generated by luminal contents and peristaltic waves of the intestine, and stiffness attributed to the extracellular matrix. These forces play critical roles in the regulation of cell proliferation, differentiation, and migration. Many efforts have been made to simulate the actual intestinal environment in vitro. The three-dimensional organoid culture system has emerged as a powerful tool for studying the mechanism of the intestinal epithelial barrier, mimicking rapidly renewing epithelium from intestinal stem cells (ISCs) in vivo. However, many aspects of how mechanical forces, such as shear stress, stiffness, compression, and stretch forces, influence the intestinal area remain unresolved. Here, we review the recent studies elucidating the impact of mechanical forces on intestinal immunity, interaction with the gut microbiome, and intestinal diseases.

Resistant starch (RS) has been shown to modulate intestinal microbiota in animal models in ways that could reduce the effects of dysbiosis-related diseases. However, the mechanism of how this is achieved is not understood. The present study aimed to reveal the mechanism of how RS mitigates dextran sulfate sodium (DSS)-induced colitis in mice by using a starch-lipid complex (RS type 5), with an RS type 2 from high-amylose maize starch as a comparison. Both RS5 and RS2 induced changes in the diversity and composition of the gut bacteria, leading to the alleviation of the induced colitis symptoms including decreasing the loss in body weight, disease activity index score, and colonic shortening. The levels of inflammatory cytokines were modulated and accompanied by an increase in goblet cell numbers and thickening of the intestinal mucus layer. RS5 was more effective, compared to RS2, in alleviating all of the colitis symptoms, mainly through improving the gut microflora dysbiosis and stimulating the generation of short-chain fatty acids (SCFAs). Our study shows that RS5 could effectively alleviate the symptoms of colitis, highlighting a potential use for RS5, particularly in relieving inflammatory bowel disease.

There are few studies about the differences in the composition of moisture, ash, crude protein, crude fat, crude polysaccharide and ergothioneine in Ganoderma lucidum spore powder (GLSP) from different origins. As for GLSP after oil extraction (OE-GLSP), there are still lots of bioactive substance in it. It can be seen that OE-GLSP has certain biological activity. The effect of OE-GLSP on the improvement of intestinal barrier function has been less studied.

The results showed that there were significant differences for GLSP from five different origins (Anhui, Jilin, Jiangxi, Shandong and Zhejiang) in moisture (0.065-0.113%), ash (0.603-0.955%), crude fat (42.444-44.773%), crude polysaccharide (2.977-4.127%), crude protein (14.761-17.639%) and ergothioneine (0.552-1.816 mg g-1) (P < 0.05). The monosaccharides of GLSP polysaccharide mainly consist of glucose, galactose, mannose, rhamnose, etc. Moreover, the effects of OE-GLSP supplementation on the regulation of organ index, colonic tissue and intestinal microbiota in C57BL/6J mice were investigated. The supplement of OE-GLSP could restore the organ index and weight loss of antibiotic-treated mice. Moreover, OE-GLSP led to the improvement of intestinal dysbiosis by enriching Bacteroidetes, Firmicutes, Lactobacillus and Roseburia, and increasing the Firmicutes/Bacteroidetes ratio. In addition, OE-GLSP intervention repaired intestinal barrier dysfunction by increasing the expression of tight junction proteins (Occludin, Claudin-1 and E-cadherin).

Different GLSP from five origins exhibited significant differences in microstructure and contents of crude polysaccharide, crude protein, crude fat, water, ash and ergothioneine. Moreover, it was found that OE-GLSP could improve the intestinal barrier function and induce potentially beneficial changes in intestinal flora. © 2024 Society of Chemical Industry.

The gut microbiota is a complex and dynamic ecosystem that plays a crucial role in human health and disease, including obesity, diabetes, cardiovascular diseases, neurodegenerative diseases, inflammatory bowel disease, and cancer. Chronic inflammation is a common feature of these diseases and is closely related to angiogenesis (the process of forming new blood vessels), which is often dysregulated in pathological conditions. Inflammation potentially acts as a central mediator. This abstract aims to elucidate the connection between the gut microbiota and angiogenesis in various diseases. The gut microbiota influences angiogenesis through various mechanisms, including the production of metabolites that directly or indirectly affect vascularization. For example, short-chain fatty acids (SCFAs) such as butyrate, propionate, and acetate are known to regulate immune responses and inflammation, thereby affecting angiogenesis. In the context of cardiovascular diseases, the gut microbiota promotes atherosclerosis and vascular dysfunction by producing trimethylamine N-oxide (TMAO) and other metabolites that promote inflammation and endothelial dysfunction. Similarly, in neurodegenerative diseases, the gut microbiota may influence neuroinflammation and the integrity of the blood-brain barrier, thereby affecting angiogenesis. In cases of fractures and wound healing, the gut microbiota promotes angiogenesis by activating inflammatory responses and immune effects, facilitating the healing of tissue damage. In cancer, the gut microbiota can either inhibit or promote tumor growth and angiogenesis, depending on the specific bacterial composition and their metabolites. For instance, some bacteria can activate inflammasomes, leading to the production of inflammatory factors that alter the tumor immune microenvironment and activate angiogenesis-related signaling pathways, affecting tumor angiogenesis and metastasis. Some bacteria can directly interact with tumor cells, activating angiogenesis-related signaling pathways. Diet, as a modifiable factor, significantly influences angiogenesis through diet-derived microbial metabolites. Diet can rapidly alter the composition of the microbiota and its metabolic activity, thereby changing the concentration of microbial-derived metabolites and profoundly affecting the host's immune response and angiogenesis. For example, a high animal protein diet promotes the production of pro-atherogenic metabolites like TMAO, activating inflammatory pathways and interfering with platelet function, which is associated with the severity of coronary artery plaques, peripheral artery disease, and cardiovascular diseases. A diet rich in dietary fiber promotes the production of SCFAs, which act as ligands for cell surface or intracellular receptors, regulating various biological processes, including inflammation, tissue homeostasis, and immune responses, thereby influencing angiogenesis. In summary, the role of the gut microbiota in angiogenesis is multifaceted, playing an important role in disease progression by affecting various biological processes such as inflammation, immune responses, and multiple signaling pathways. Diet-derived microbial metabolites play a crucial role in linking the gut microbiota and angiogenesis. Understanding the complex interactions between diet, the gut microbiota, and angiogenesis has the potential to uncover novel therapeutic targets for managing these conditions. Therefore, interventions targeting the gut microbiota and its metabolites, such as through fecal microbiota transplantation (FMT) and the application of probiotics to alter the composition of the gut microbiota and enhance the production of beneficial metabolites, present a promising therapeutic strategy.

Stroke is one of the most devastating pathologies in terms of mortality, cause of dementia, major adult disability, and socioeconomic burden worldwide. Despite its severity, treatment options remain limited, with no pharmacological therapies available for hemorrhagic stroke (HS) and only fibrinolytic therapy or mechanical thrombectomy for ischemic stroke (IS). In the pathophysiology of stroke, after the acute phase, many patients develop systemic immunosuppression, which, combined with neurological dysfunction and hospital management, leads to the onset of stroke-associated infections (SAIs). These infections worsen prognosis and increase mortality. Recent evidence, particularly from experimental studies, has highlighted alterations in the microbiota-gut-brain axis (MGBA) following stroke, which ultimately disrupts the gut flora and increases intestinal permeability. These changes can result in bacterial translocation (BT) from the gut to sterile organs, further contributing to the development of SAIs. Given the novelty and significance of these processes, especially the role of BT in the development of SAIs, this review summarizes the latest advances in understanding these phenomena and discusses potential therapeutic strategies to mitigate them, ultimately reducing post-stroke complications and improving treatment outcomes.

Recurrent C. difficile infection (CDI) is a major health threat with significant mortality and financial costs. Fecal Microbiota Transplantation (FMT) is an effective therapy, however the mechanisms by which it acts, particularly on the host, are poorly understood. Here we enrolled a prospective cohort of human patients with recurrent CDI (n=16) undergoing FMT therapy. Colonic biopsies were collected and bulk RNA sequencing was performed to compare changes in host gene expression pre- and two months post-FMT. Transcriptional profiles were significantly altered after FMT therapy, with many differentially expressed genes (~15% of annotated genes detected). Enrichment analysis determined that these changes were reflective of increased protein production post-FMT, with enrichment of pathways such as Ribosome Biogenesis, Protein Processing, and signaling pathways (Myc, mTORc1, E2F) associated with cell proliferation and protein biosynthesis. Histology of H&E-stained biopsies identified a significant increase in colonic crypt length post-FMT, suggesting that this treatment promotes cell proliferation. Crypt length was significantly correlated with enriched Myc and mTOR signaling pathways as well as genes associated with polyamine biosynthesis, providing a potential mechanism through which this may occur. Finally, signaling pathways upstream of Myc and mTOR, notably IL-33 Signaling and EGFR ligands, were significantly upregulated, suggesting that FMT may utilize these signals to promote cell proliferation and restoration of the intestine.

The gut microbiota metabolizes flavonoids, amino acids, dietary fiber, and other components of foods to produce a variety of gut microbiota-derived metabolites. Flavonoids are the largest group of polyphenols, and approximately 7000 flavonoids have been identified. A variety of phenolic acids are produced from flavonoids and amino acids through metabolic processes by the gut microbiota. Furthermore, these phenolic acids are easily absorbed. Phenolic acids generally represent phenolic compounds with one carboxylic acid group. Gut microbiota-derived phenolic acids have antiviral effects against several viruses, such as SARS-CoV-2 and influenza. Furthermore, phenolic acids influence the immune system by inhibiting the secretion of proinflammatory cytokines, such as interleukin-1β and tumor necrosis factor-α. In the nervous systems, phenolic acids may have protective effects against neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases. Moreover, phenolic acids can improve levels of blood glucose, cholesterols, and triglycerides. Phenolic acids also improve cardiovascular functions, such as blood pressure and atherosclerotic lesions. This review focuses on the current knowledge of the effects of phenolic acids produced from food-derived flavonoids and amino acids by the gut microbiota on health and disease.

The disease resistance phenotype is closely related to immunomodulatory function and immune tolerance and has far-reaching implications in animal husbandry and human health. Microbes play an important role in the initiation, prevention, and treatment of diseases, but the mechanisms of host-microbiota interactions in disease-resistant phenotypes are poorly understood. In this study, we hope to uncover and explain the role of microbes in intestinal diseases and their mechanisms of action to identify new potential treatments.

First, we established the colitis model of DSS in two breeds of sheep and then collected the samples for multi-omics testing including metagenes, metabolome, and transcriptome. Next, we made the fecal bacteria liquid from the four groups of sheep feces collected from H-CON, H-DSS, E-CON, and E-DSS to transplant the fecal bacteria into mice. H-CON feces were transplanted into mice named HH group and H-DSS feces were transplanted into mice named HD group and Roseburia bacteria treatment named HDR groups. E-CON feces were transplanted into mice named EH group and E-DSS feces were transplanted into mice in the ED group and Roseburia bacteria treatment named EDR groups. After successful modeling, samples were taken for multi-omics testing. Finally, colitis mice in HD group and ED group were administrated with Roseburia bacteria, and the treatment effect was evaluated by H&E, PAS, immunohistochemistry, and other experimental methods.

The difference in disease resistance of sheep to DSS-induced colitis disease is mainly due to the increase in the abundance of Roseburia bacteria and the increase of bile acid secretion in the intestinal tract of Hu sheep in addition to the accumulation of potentially harmful bacteria in the intestine when the disease occurs, which makes the disease resistance of Hu sheep stronger under the same disease conditions. However, the enrichment of harmful microorganisms in East Friesian sheep activated the TNFα signalling pathway, which aggravated the intestinal injury, and then the treatment of FMT mice by culturing Roseburia bacteria found that Roseburia bacteria had a good curative effect on colitis.

Our study showed that in H-DSS-treated sheep, the intestinal barrier is stabilized with an increase in the abundance of beneficial microorganisms. Our data also suggest that Roseburia bacteria have a protective effect on the intestinal barrier of Hu sheep. Accumulating evidence suggests that host-microbiota interactions are associated with IBD disease progression. Video Abstract.

The crucial role of gut microbiota in shaping immunotherapy outcomes has prompted investigations into potential modulators. Here we show that oral administration of acarbose significantly increases the anti-tumour response to anti-PD-1 therapy in female tumour-bearing mice. Acarbose modulates the gut microbiota composition and tryptophan metabolism, thereby contributing to changes in chemokine expression and increased T cell infiltration within tumours. We identify CD8+ T cells as pivotal components determining the efficacy of the combined therapy. Further experiments reveal that acarbose promotes CD8+ T cell recruitment through the CXCL10-CXCR3 pathway. Faecal microbiota transplantation and gut microbiota depletion assays indicate that the effects of acarbose are dependent on the gut microbiota. Specifically, acarbose enhances the efficacy of anti-PD-1 therapy via the tryptophan catabolite indoleacetate, which promotes CXCL10 expression and thus facilitates CD8+ T cell recruitment, sensitizing tumours to anti-PD-1 therapy. The bacterial species Bifidobacterium infantis, which is enriched by acarbose, also improves response to anti-PD-1 therapy. Together, our study endorses the potential combination of acarbose and anti-PD-1 for cancer immunotherapy.

The biosafety concerns associated with fecal microbiota transplant (FMT) limit their clinical application in treating ulcerative colitis (UC). Gut microbiota secrete abundant extracellular vesicles (Gm-EVs), which play a critical role in bacteria-to-bacteria and bacteria-to-host communications. Herein, intestinal microbiota are trained using tea leaf lipid/pluronic F127-coated curcumin nanocrystals (CN@Lp127s), which can maintain stability during transit through the gastrointestinal tract. Compared with FMT, Gm-EVs derived from healthy mice significantly improve treatment outcomes against UC by reducing colonic inflammatory responses, restoring colonic barrier function, and rebalancing intestinal microbiota. Strikingly, Gm-EVs obtained from CN@Lp127-trained healthy mice exhibit a superior therapeutic effect on UC compared to groups receiving FMT from healthy mice, Gm-EVs from healthy mice, and FMT from CN@Lp127-trained healthy mice. Oral administration of Gm-EVs from CN@Lp127-trained healthy mice not only alleviates colonic inflammation, promotes mucosal repair, and regulates gut microbiota but also regulates purine metabolism to decrease the uric acid level, resulting in a robust improvement in the UC. This study demonstrates the UC therapeutic efficacy of Gm-EVs derived from nanomedicine-trained gut microbiota in regulating the immune microenvironment, microbiota, and purine metabolism of the colon. These EVs provide an alternative platform to replace FMT as a treatment for UC.

Isoorientin (ISO) is a naturally occurring flavonoid with diverse functional properties that mitigate the risk of diseases stemming from oxidation, inflammation, and cancer cell proliferation. P-glycoprotein (P-gp) is a vital component of the intestinal epithelium and may play a role in the onset of intestinal inflammatory conditions, such as inflammatory bowel disease (IBD). Recent studies have suggested that short-chain fatty acids (SCFAs) and secondary bile acids (SBAs) produced by the gut microbiota stimulate the increase of P-gp expression, alleviating excessive inflammation and thereby preservation of intestinal homeostasis. ISO has been shown to improve colon health and modulate the gut microbiota. In this study, we aimed to explore whether ISO can modulate the microbes and their metabolites to influence P-gp expression to alleviate IBD. First, the impact of ISO on dextran sulfate sodium (DSS)-treated colitis in mice was investigated. Second, 16S rRNA gene sequencing was conducted. The present study indicated that ISO mitigated the symptoms and pathological damage associated with DSS-treated colitis in mice. Western blot analysis revealed ISO upregulated P-gp in colon tissues, suggesting the critical role of P-gp protein in intestinal epithelial cells. 16S microbial diversity sequencing revealed ISO restored the richness and variety of intestinal microorganisms in colitis-bearing mice and enriched SCFA-producing bacteria, such as Lachnospiraceae_NK4A136_group. The experiments also revealed that the ISO fecal microbiota transplantation (FMT) inoculation of DSS-treated mice had similarly beneficial results. FMT mice showed a reduction in colitis symptoms, which was more pronounced in ISO-FMT than in CON-FMT mice. Meanwhile, ISO-FMT expanded the abundance of beneficial microorganisms, increased the expression of metabolites, such as SCFAs and total SBAs, and significantly upregulated the expression of P-gp protein. In addition, Spearman's correlation analysis demonstrated a positive correlation between the production of SCFAs and SBAs and the expression of P-gp. The present study identified that ISO increases the expression of P-gp in the intestinal epithelium by regulating intestinal microorganisms and their metabolites, which maintains colonic homeostasis, improves the integrity of the colonic epithelium, and alleviates colitis.

Food allergy (FA) is a common disorder in children and affects the health of children worldwide. The gut microbiota is closely related to the occurrence and development of FA. Fecal microbiota transplantation (FMT) is a way to treat diseases by reconstituting the microbiota; however, the role and mechanisms of FA have not been validated.

In this study, we established an ovalbumin (OVA)-induced juvenile mouse model and used 16S RNA sequencing, pathological histological staining, molecular biology, and flow-through techniques to evaluate the protective effects of FMT treatment on FA and to explore the mechanisms.

OVA-induced dysregulation of the gut microbiota led to impaired intestinal function and immune dysregulation in FA mice. FMT treatment improved the structure, diversity, and composition of the gut microbiota and restored it to a near-donor state. FMT treatment reduced levels of Th2-associated inflammatory factors, decreased intestinal tissue inflammation, and reduced IgE production. In addition, FMT reduced the number of mast cells and eosinophils and suppressed OVA-specific antibodies. Further mechanistic studies revealed that FMT treatment induced immune tolerance by inducing the expression of CD103+DCs and programmed cell death ligand 1 (PD-L1) in mesenteric lymph nodes and promoting the production of Treg through the programmed cell death protein 1 (PD-1)/PD-L1 pathway. Meanwhile, Th2 cytokines, OVA-specific antibodies, and PD-1/PD-L1 showed a significant correlation with the gut microbiota.

FMT could regulate the gut microbiota and Th1/Th2 immune balance and might inhibit FA through the PD-1/PD-L1 pathway, which would provide a new idea for the treatment of FA.

The fecal microbiome is identical to the gut microbial communities and provides an easy access to the gut microbiome. Therefore, fecal microbial transplantation (FMT) strategies have been used to alter dysbiotic gut microbiomes with healthy fecal microbiota, successfully alleviating various metabolic disorders, such as obesity, type 2 diabetes, and inflammatory bowel disease (IBD). However, the success of FMT treatment is donor-dependent and variations in gut microbes cannot be avoided. This problem may be overcome by using a cultured fecal microbiome. In this study, a human fecal microbiome was cultured using five different media; growth in brain heart infusion (BHI) media resulted in the highest microbial community cell count. The microbiome (16S rRNA) data demonstrated that the cultured microbial communities were similar to that of the original fecal sample. Therefore, the BHI-cultured fecal microbiome was selected for cultured FMT (cFMT). Furthermore, a dextran sodium sulfate (DSS)-induced mice-IBD model was used to confirm the impact of cFMT. Results showed that cFMT effectively alleviated IBD-associated symptoms, including improved gut permeability, restoration of the inflamed gut epithelium, decreased expression of pro-inflammatory cytokines (IFN-γ, TNF-α, IL-1, IL-6, IL-12, and IL-17), and increased expression of anti-inflammatory cytokines (IL-4 and IL-10). Thus, study's findings suggest that cFMT can be a potential alternative to nFMT. KEY POINTS: • In vitro fecal microbial communities were grown in a batch culture using five different media. • Fecal microbial transplantation was performed on DSS-treated mice using cultured and normal fecal microbes. • Cultured fecal microbes effectively alleviated IBD-associated symptoms.

Alterations to the gut microbiota are associated with ulcerative colitis (UC), whereas restoration of normobiosis can effectively alleviate UC. l-Theanine has been shown to reshape the gut microbiota and regulate gut immunity. To investigate the mechanisms by which l-theanine alleviates UC, we used l-theanine and l-theanine fecal microbiota solution to treat UC mice. In this study, we used l-theanine and l-theanine fecal microbiota solution to treat UC mice to explore the mechanism by which l-theanine alleviates UC. By reducing inflammation in the colon, we demonstrated that l-theanine alleviates symptoms of UC. Meanwhile, l-theanine can improve the abundance of microbiota related to short-chain fatty acid, bile acid, and tryptophan production. Single-cell sequencing results indicated that l-theanine-mediated suppression of UC was associated with immune cell changes, especially regarding macrophages and T and B cells, and validated the immune cell responses to the gut microbiota. Further, flow cytometry results showed that the ability of dendritic cells, macrophages, and monocytes to present microbiota antigens to colonic T cells in an MHC-II-dependent manner was reduced after treating normal mouse fecal donors with l-theanine. These results demonstrate that l-theanine modulates colon adaptive and innate immunity by regulating the gut microbiota in an MHC-II-dependent manner, thereby alleviating UC.

Rationale: Macrophage polarization plays an important role in the inflammatory regulation of ulcerative colitis (UC). In this context, necroptosis is a type of cell death that regulates intestinal inflammation, and selenoprotein S (SelS) is a selenoprotein expressed in intestinal epithelial cells and macrophages that prevents intestinal inflammation. However, the underlying mechanisms of SelS in both cell types in regulating UC inflammatory responses remain unclear. Therefore, the direct effect of SelS deficiency on necroptosis in colonic epithelial cells (CECs) was investigated. In addition, whether SelS knockdown exacerbated intestinal inflammation by modulating macrophage polarization to promote necroptosis in CECs was assessed. Methods: The UC model of SelS knockdown mice was established with 3.5% sodium dextran sulfate, and clinical indicators and colon injury were evaluated in the mice. Moreover, SelS knockdown macrophages and CECs cultured alone/cocultured were treated with IL-1β. The M1/M2 polarization, NF-κB/NLRP3 signaling pathway, oxidative stress, necroptosis, inflammatory cytokine, and tight junction indicators were analyzed. In addition, co-immunoprecipitation, liquid chromatography-mass spectrometry, laser confocal analysis, and molecular docking were performed to identify the interacting proteins of SelS. The GEO database was used to assess the correlation of SelS and its target proteins with macrophage polarization. The intervention effect of four selenium supplements on UC was also explored. Results: Ubiquitin A-52 residue ribosomal protein fusion product 1 (Uba52) was identified as a potential interacting protein of SelS and SelS, Uba52, and yes-associated protein (YAP) was associated with macrophage polarization in the colon tissue of patients with UC. SelS deficiency in CECs directly induced reactive oxygen species (ROS) production, necroptosis, cytokine release, and tight junction disruption. SelS deficiency in macrophages inhibited YAP ubiquitination degradation by targeting Uba52, promoted M1 polarization, and activated the NF-κB/NLRP3 signaling pathway, thereby exacerbating ROS-triggered cascade damage in CECs. Finally, exogenous selenium supplementation could effectively alleviate colon injury in UC. Conclusion: SelS is required for maintaining intestinal homeostasis and that its deletion enhances necroptosis in CECs, which is further exacerbated by promoting M1 macrophage polarization, and triggers more severe barrier dysfunction and inflammatory responses in UC.

Inflammatory bowel disease (IBD) is an immune system disorder primarily characterized by colitis, the exact etiology of which remains unclear. Traditional treatment approaches currently yield limited efficacy and are associated with significant side effects. Extensive research has indicated the potent therapeutic effects of probiotics, particularly Lactobacillus strains, in managing colitis. However, the mechanisms through which Lactobacillus strains ameliorate colitis require further exploration. In our study, we selected Lactobacillus gasseri ATCC33323 from the intestinal microbiota to elucidate the specific mechanisms involved in modulation of colitis. Experimental findings in a DSS-induced colitis mouse model revealed that L. gasseri ATCC33323 significantly improved physiological damage in colitic mice, reduced the severity of colonic inflammation, decreased the production of inflammatory factors, and preserved the integrity of the intestinal epithelial structure and function. It also maintained the expression and localization of adhesive proteins while improving intestinal barrier permeability and restoring dysbiosis in the gut microbiota. E-cadherin, a critical adhesive protein, plays a pivotal role in this protective mechanism. Knocking down E-cadherin expression within the mouse intestinal tract significantly attenuated the ability of L. gasseri ATCC33323 to regulate colitis, thus confirming its protective role through E-cadherin. Finally, transcriptional analysis and in vitro experiments revealed that L. gasseri ATCC33323 regulates CDH1 transcription by affecting NR1I3, thereby promoting E-cadherin expression. These findings contribute to a better understanding of the specific mechanisms by which Lactobacillus strains alleviate colitis, offering new insights for the potential use of L. gasseri as an alternative therapy for IBD, particularly in dietary supplementation.

Invariant natural killer T (iNKT) cells are immune cells that harness properties of both the innate and adaptive immune system and exert multiple functions critical for the control of various diseases. Prevention of graft-versus-host disease (GVHD) by iNKT cells has been demonstrated in mouse models and in correlative human studies in which high iNKT cell content in the donor graft is associated with reduced GVHD in the setting of allogeneic hematopoietic stem cell transplants. This suggests that approaches to increase the number of iNKT cells in the setting of an allogeneic transplant may reduce GVHD. iNKT cells can also induce cytolysis of tumor cells, and murine experiments demonstrate that activating iNKT cells in vivo or treating mice with ex vivo expanded iNKT cells can reduce tumor burden. More recently, research has focused on testing anti-tumor efficacy of iNKT cells genetically modified to express a chimeric antigen receptor (CAR) protein (CAR-iNKT) cells to enhance iNKT cell tumor killing. Further, several of these approaches are now being tested in clinical trials, with strong safety signals demonstrated, though efficacy remains to be established following these early phase clinical trials. Here we review the progress in the field relating to role of iNKT cells in GVHD prevention and anti- cancer efficacy. Although the iNKT field is progressing at an exciting rate, there is much to learn regarding iNKT cell subset immunophenotype and functional relationships, optimal ex vivo expansion approaches, ideal treatment protocols, need for cytokine support, and rejection risk of iNKT cells in the allogeneic setting.

Metabolic dysfunction-associated steatohepatitis (MASH) is an inflammatory subtype of metabolic dysfunction-associated steatotic liver disease (MASLD) has recently been proposed as a replacement term for NAFLD, a common, multifactorial and poorly understood liver disease whose incidence is increasing worldwide. In recent years, there has been increasing scientific interest in exploring the relationship between gut microbiota and MASH. To learn more about the gut microbiota in MASH, this study aims to provide a comprehensive analysis of the knowledge structure and research hotspots from a bibliometric perspective.

We searched the Web of Science Core Collection for articles and reviews that covered the connections between gut microbiota and MASH over the last decade. The Online Analysis Platforms, VOSviewer, CiteSpace, the R tool "bibliometrix" were used to analyzed existing publications trends and hotspots.

A total of 4,069 documents related to the interaction between gut microbiota and MASH were retrieved from 2014 to 2023. The number of annual publications increased significantly over the last decade, particularly in the United States and China. The University of California-San Diego was the most productive institution, while researcher Rohit Loomba published the most papers in the field. Younossi ZM was ranked as the first co-cited author and largest contributor of highly cited articles in the field. Gastroenterology and hepatology were the most common specialty category. The most cited journal in the last decade was Hepatology. The Keyword Bursts analysis highlighted the importance of studying the association between gut microbiota and MASH, as well as related factors such as metabolic syndrome, insulin resistance, endotoxemia and overgrowth of gut bacteria. Keyword clusters with co-citation were used to illustrate important topics including intestinal permeability, insulin sensitivity and liver immunology. The most common keywords include insulin resistance, obesity, dysbiosis, inflammation and oxidative stress, which are current hotspots.

Our analysis highlights key aspects of this field and emphasizes multiorgan crosstalk in MASLD/MASH pathogenesis. In particular, the central role of the gut-liver axis and the significant influence of gut microbiota dysbiosis on disease progression are highlighted. Furthermore, our results highlight the transformative potential of microbiota-specific therapies and cover the way for innovative healthcare and pharmaceutical strategies.

The role of infections in the pathogenesis of autoimmune diseases has long been recognized and reported. In addition to infectious agents, the internal composition of the "friendly" living bacteria, (microbiome) and its correlation to immune balance and dysregulation have drawn the attention of researchers for decades. Nevertheless, only recently, scientific papers regarding the potential role of transferring microbiome from healthy donor subjects to patients with autoimmune diseases has been proposed. Fecal microbiota transplantation or FMT, carries the logic of transferring microorganisms responsible for immune balance from healthy donors to individuals with immune dysregulation or more accurately for our paper, autoimmune diseases. Viewing the microbiome as a pathogenetic player allows us to consider FMT as a pathogenetic-based treatment. Promising results alongside improved outcomes have been demonstrated in patients with different autoimmune diseases following FMT. Therefore, in our current extensive review, we aimed to highlight the implication of FMT in various autoimmune diseases, such as inflammatory bowel disease, autoimmune thyroid and liver diseases, systemic lupus erythematosus, and type 1 diabetes mellitus, among others. Presenting all the aspects of FMT in more than 12 autoimmune diseases in one paper, to the best of our knowledge, is the first time presented in medical literature. Viewing FMT as such could contribute to better understanding and newer application of the model in the therapy of autoimmune diseases, indeed.

Aflatoxin B1 (AFB1) is one of the most widespread contaminants in agricultural commodities. Pleurotus eryngii (PE) is widely used as a feed additive for its anti-inflammatory properties, and its major active substance is believed to be polysaccharides. This study aims to explore the underlying mechanism of dietary PE polysaccharides alleviating AFB1-induced toxicity in ducks. The major monosaccharide components of PE polysaccharides were identified as glucose, mannose, galactose, glucuronic acid, and fucose. The results showed that dietary PE polysaccharides could alleviate liver inflammation, alleviate intestinal barrier dysfunction, and change the imbalanced gut microbiota induced by AFB1 in ducks. However, PE polysaccharides failed to exert protective roles on the liver and intestine injury induced by AFB1 in antibiotic-treated ducks. The PE + AFB1-originated microbiota showed a positive effect on intestinal barrier and inflammation, the SCFAs transport via the gut-liver axis, and liver inflammation compared with the AFB1-originated microbiota in ducks. These findings provided a possible mechanism that PE polysaccharides alleviated AFB1-induced liver inflammation in ducks by remodeling gut microbiota, regulating microbiota-derived SCFAs transport via the gut-liver axis, and inhibiting inflammatory gene expressions in the liver, which may provide new insight for therapeutic methods against AFB1 exposure in animals.

Chinese liquor distillers' grain (CLDG) is a valuable and abundant by-product from traditional Chinese baijiu production, containing a diverse array of bioactive components that have attracted significant interest. Herein, a water-soluble polysaccharide, DGPS-2B, with a weight-average molecular weight of 37.3 kDa, was isolated from the alkali-extract fraction of CLDG. Methylation and NMR analysis identified that the primary constituents of DGPS-2B are arabinoxylans, with an arabinose-to-xylose ratio of 0.66. In an animal model of colitis, DGPS-2B treatment significantly altered the gut microbiota composition by increasing the SCFA-producing bacteria (e.g., Butyricicoccus) and reducing the mucin-degrading bacteria such as Muribaculaceae. This microbial shift resulted in elevated production of butyrate, acetate, and propionate, which subsequently suppressed NF-κB signaling, decreased the levels of IL-1β, IL-6, and TNFα, and potentially inactivated Notch signaling. These multifaceted effects stimulated mucin 2 production, reduced inflammation and apoptosis in the gut epithelium, and ultimately alleviated colitis symptoms. Collectively, this study not only elucidates the purification and characterization of DGPS-2B from CLDG but also illuminates its anti-colitic properties and the underlying molecular mechanisms. These findings underscore the potential of DGPS-2B as a therapeutic intervention for managing inflammatory bowel disease and emphasize CLDG as a promising source for developing value-added products.

Egg yolk lipids significantly alleviate dextran sulfate sodium (DSS)-induced colitis by inhibiting NLRP3 inflammasome, reversing gut microbiota dysbiosis, and increasing short chain fatty acids (SCFAs) concentrations. However, the role of gut microbiota and the relationship between SCFAs and NLRP3 inflammasome are still unknown. Here, this study confirms that antibiotic treatment abolishes the protective effect of egg yolk lipids on DSS-induced colonic inflammation, intestinal barrier damage, and lipopolysaccharide translocation. Fecal microbiota transplantation also supports that egg yolk lipids alleviate colitis in a gut microbiota-dependent manner. Then, the study investigates the relationship between SCFAs and NLRP3 inflammasome, and finds that SCFAs significantly suppress colitis via inhibiting colonic NLRP3 inflammasome activation and proinflammatory cytokines secretions (interleukin, IL)-1β and IL-18, and combined treatment of SCFAs and MCC950 (NLRP3 inhibitor) shows a better activity against colitis and NLRP3 inflammasome activation. Together, these findings provide positive evidence for gut microbiorta-SCFAs-NLRP3 axis as a novel target involving in the therapy of inflammatory bowel disease.

The role of the intestinal microbiota in the diagnosis and treatment of pancreatic diseases is increasingly significant. Consequently, fecal microbiota transplantation (FMT) is emerging as a promising therapeutic avenue for various pancreatic disorders, including cancer, pancreatitis, and type 1 diabetes (T1D). This innovative procedure entails transferring gut microbiota from healthy donors to individuals affected by pancreatic ailments with the potential to restore intestinal balance and alleviate associated symptoms. FMT represents a pioneering approach to improve patient outcomes in pancreatic diseases, offering tailored treatments customized to individual microbiomes and specific conditions. Recent research highlights the therapeutic benefits of targeting the gut microbiota for personalized interventions in pancreatic disorders. However, a comprehensive understanding of the intricate interplay between gut microbiota and pancreatic physiology warrants further investigation. The necessity for additional studies and research endeavors remains crucial, especially in elucidating both adult and pediatric cases affected by pathological pancreatic conditions.

Diarrhea-induced mortality among juvenile yaks is highly prevalent in the pastoral areas of the Qinghai-Tibet plateau. Although numerous diseases have been linked to the gut microbial community, little is known about how diarrhea affects the gut microbiota in yaks. In this work, we investigated and compared changes in the gut microbiota of juvenile yaks with diarrhea. The results demonstrated a considerable drop in the alpha diversity of the gut microbiota in diarrheic yaks, accompanied by Eysipelatoclostridium, Parabacteroides, and Escherichia-Shigella, which significantly increased during diarrhea. Furthermore, a PICRust analysis verified the elevation of the gut-microbial metabolic pathways in diarrhea groups, including glycine, serine, and threonine metabolism, alanine, aspartate, oxidative phosphorylation, glutamate metabolism, antibiotic biosynthesis, and secondary metabolite biosynthesis. Taken together, our study showed that the harmful bacteria increased, and beneficial bacteria decreased significantly in the gut microbiota of yaks with diarrhea. Moreover, these results also indicated that the dysbiosis of the gut microbiota may be a significant driving factor of diarrhea in yaks.